RESUMO
The role of contact system activation has been clearly established in the pathogenesis of hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH). C1 inhibitor (C1INH)-protease complexes, levels of functional C1INH, plasma kallikrein activation, and cleavage of high-molecular-weight kininogen have each been associated with disease activity. More recently, HAE with normal levels of C1INH (HAE-nl-C1INH) has been recognized. Six genetic mutations have been identified which are linked to HAE-nl-C1INH phenotypes. The majority of individuals with HAE-nl-C1INH fall into the unknown category. There is substantial evidence that bradykinin generation underlies the recurrent attacks of swelling in some of these cohorts.
Assuntos
Biomarcadores , Bradicinina , Proteína Inibidora do Complemento C1 , Humanos , Bradicinina/metabolismo , Proteína Inibidora do Complemento C1/metabolismo , Angioedema/diagnóstico , Angioedema/metabolismo , Angioedema/etiologia , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/metabolismo , Angioedemas Hereditários/etiologia , MutaçãoRESUMO
Hereditary angioedema (HAE) is a rare autosomal genetic disease for which there are currently nine FDA-approved drugs. This review summarizes drug treatments for HAE based on four therapeutic pathways: inhibiting the contact system, inhibiting bradykinin binding to B2 receptors, supplying missing C1 inhibitors, and inhibiting plasminogen conversion. The review generalizes the clinical use, pharmacological effects and mechanisms of HAE drugs, and it also discusses possible development directions and targets to enhance understanding of HAE and help researchers.